Enteric Glial Dysfunction Evoked by Apolipoprotein E Deficiency Contributes to Delayed Gastric Emptying.

Area of Science:

• Neuroscience
• Gastroenterology
• Cell Biology

Background:

• Diabetes mellitus is a primary cause of gastroparesis, characterized by reduced neuronal nitric oxide synthase (nNOS) in the stomach's myenteric ganglia.
• Defects in apolipoprotein E (ApoE), a neuroprotective protein secreted by astrocytes, can also lead to decreased nNOS expression.
• The specific roles of ApoE and enteric glial cells in regulating gastric motility remain unclear.

Purpose of the Study:

• To investigate the alterations in apolipoprotein E (ApoE) and enteric glial cells in the context of diabetic gastroparesis.
• To determine the impact of ApoE deficiency and enteric glial cell changes on gastric motility.
• To evaluate the therapeutic potential of neural stem cell (NSC) transplantation for restoring gastric function.

Main Methods:

• Analysis of type 2 diabetic (db/db) mice and apolipoprotein E-knockout (ApoE-/-) mice.
• Measurement of gastric emptying using the ¹³C acetic acid breath test.
• Immunohistochemical examination of glial fibrillary acidic protein (GFAP) and protein gene product 9.5 (PGP 9.5) expression.
• Intragastric transplantation of neural stem cells (NSCs) into ApoE-/- mice.

Main Results:

• Delayed gastric emptying was observed in 27% of db/db mice, accompanied by reduced serum ApoE and gastric GFAP expression.
• ApoE-/- mice exhibited delayed gastric emptying and significantly decreased GFAP expression, without alterations in PGP 9.5.
• Transplantation of NSCs successfully improved gastric emptying in ApoE-/- mice by increasing GFAP-positive cells.

Conclusions:

• Reduced enteric glial cells, associated with ApoE deficiency, play a critical role in the development of delayed gastric emptying.
• Neural stem cell (NSC) transplantation demonstrates efficacy in restoring myenteric ganglia and improving gastric motility in gastroparesis models.